Ene Reaction Research Articles

Regioselective and Stereoselective Synthesis of Parthenolide Analogs by Acyl Nitroso-Ene Reaction and Their Biological Evaluation against Mycobacterium tuberculosis.

Historically, natural products have played a major role in the development of antibiotics. Their complex chemical structures and high polarity give them advantages in the drug discovery process. In the broad range of natural products, sesquiterpene lactones are interesting compounds because of their diverse biological activities, their high-polarity, and sp3-carbon-rich chemical structures. Parthenolide (PTL) is a natural compound isolated from Tanacetum parthenium, of the family of germacranolide-type sesquiterpene lactones. In recent years, parthenolide has been studied for its anti-inflammatory, antimigraine, and anticancer properties. Recently, PTL has shown antibacterial activities, especially against Gram-positive bacteria. However, few studies are available on the potential antitubercular activities of parthenolide and its analogs. It has been demonstrated that parthenolide's biological effects are linked to the reactivity of α-exo-methylene-γ-butyrolactone, which reacts with cysteine in targeted proteins via a Michael addition. In this work, we describe the ene reaction of acylnitroso intermediates with parthenolide leading to the regioselective and stereoselective synthesis of new derivatives and their biological evaluation. The addition of hydroxycarbamates and hydroxyureas led to original analogs with higher polarity and solubility than parthenolide. Through this synthetic route, the Michael acceptor motif was preserved and is thus believed to be involved in the selective activity against Mycobacterium tuberculosis.

Platform for the Immobilizing of Ultrasmall Pd Clusters for Carbonylation: In Situ Self-Templating Fabrication of ZIF-8 on ZnO.

Incorporating metal clusters into the confined cavities of metal-organic frameworks (MOFs) to form MOF-supported catalysts has attracted considerable research interest with regard to carbonylation reactions. Herein, a self-templating method is used to prepare the zinc oxide (ZnO)-supported core-shell catalyst ZnO@Pd/ZIF-8. This facile strategy controls the growth of metal sources on the ZIF-8 shell layer and avoids the metal diffusion or aggregation problems of the conventional synthesis method. The characteristics of the catalysts show that the palladium (Pd) clusters are highly dispersed with an average particle size of ≈1.2nm, making them excellent candidates as a catalyst for carbonylation under mild conditions. The optimal catalyst (1.25-ZnO@Pd/ZIF-8) exhibits excellent activity in synthesizing α, β-alkynyl ketones under 1 atm of carbon monooxide (CO), and the conversion rate of 1, 3-diphenylprop-2-yn-1-one is 3.09 and 3.87 times more than those of Pd/ZIF-8 and Pd2+, respectively, for the first 2h. Moreover, the 1.25-ZnO@Pd/ZIF-8 is recyclable, showing negligible metal leaching, and, under the conditions used in this investigation, can be reused at least five times without considerable loss in its catalytic efficiency. This protocol can also be applied with other nucleophile reagents to synthesize esters, amides, and acid products.

Adaptable Networks with Semiorthogonal Two-Stage Polymerizations Enabled by Sequential Photoinitiated Thiol–Ene and Disulfide–Ene Reactions

Adaptable Networks with Semiorthogonal Two-Stage Polymerizations Enabled by Sequential Photoinitiated Thiol–Ene and Disulfide–Ene Reactions

Synthetic studies toward Swinhoeisterol A: Synthesis of the 6/6/5/7 tetracyclic core

6/6/5/7 Tetracyclic core of Swinhoeisterol A was constructed starting from Wieland-Miescher ketone and silylated ethyl 5–hydroxyvalerate. After modification, the bicyclic and linear subunits were assembled by means of cross-metathesis reaction. Then, cyclopentane C ring was formed by the intramolecular aldol condensation. C17-stereocenter was constructed using Claisen rearrangement followed by the decarbonylation step. Finally, ene reaction was applied for the simultaneous formation of cycloheptane d-ring and tetrasubstituted double bond between rings B and C.

Recent Advances in Catalytic Carbonylation Reactions in Alternative Reaction Media

Comprehensive SummarySince the discovery of the hydroformylation (oxo‐synthesis or Roelen reaction) and the Reppe‐reaction, the transition metal‐catalyzed carbonylation reactions, providing versatile, facile, and even atom‐economic methods for the selective incorporation of C=O functionality to various skeletons, have gained tremendous importance in synthetic organic chemistry from laboratories to industrial applications. The carbonylation of carbon‐carbon multiple bonds, aromatic halides, triflates, etc., in the presence of various nucleophiles has led the way to produce aldehydes, carboxylic acids, esters, amides, etc., in the fine chemical industry. However, these protocols usually proceed in conventional, fossil‐based, and usually toxic reaction environments. Thus, several attempts have been directed to developing efficient carbonylation methods in alternative, less harmful, non‐fossil‐based and even in renewable reaction media. In this review, we overview the recent applications of alternative solvents such as water, biomass‐based alcohols, γ‐valerolactone (GVL), 2‐methyltetrahydrofuran (2‐MeTHF), ionic liquids (ILs), deep eutectic solvents (DES), alkyl levulinates, limonene, α‐pinene, and dimethyl carbonate as well as fluorous media to improve efficiency, safety and environmentally benign nature of carbonylation protocols.

Palladium-Catalyzed Tandem Cyclization of Bromoalkynes, Anilines and CO: Access to 1,3-Substituted Maleimides.

A novel palladium-catalyzed three-component carbonylation reaction for the assembly of various 1,3-substituted maleimide derivatives from haloalkynes and simple anilines. The nucleophilic addition reaction of haloalkynes, anilines and CO, and insertion of carbonyl have been achieved sequentially in this reaction. The high chemo- and regioselectivities, as well as no need of expensive ligands or additives further illustrate the synthetic value of this approach.

Singlet oxygen-mediated fluconazole degradation during the activation of chlorine dioxide with sulfite

Singlet oxygen (1O2)-mediated advanced oxidations have received considerable attention due to their strong capacity to resist the water matrix and high selectivity for organic pollutants. In this study, the activation of chlorine dioxide with sulfite (sulfite/ClO2 process) to effectively produce 1O2 was proposed to degrade fluconazole (FLC) and simultaneously control the formation of disinfection byproducts (DBPs). The results revealed that FLC could be rapidly degraded by 78.6 % within 10 s by the sulfite/ClO2 process. Radical quenching tests and electron paramagnetic resonance (EPR) measurements confirm that 1O2 produced by the cleavage of epoxides formed by the combination of triazole electron-rich groups in FLC with peroxymonosulfate (PMS) was the main active species in the sulfite/ClO2 process. The degradation of FLC was favored under alkaline conditions because of the fast electron transfer rate at higher pH values. The presence of chloride (Cl−), bicarbonate (HCO3−), and humic acid (HA) hindered the degradation of FLC mainly because they compete with PMS for the electron-rich groups produced by the reaction. The degradation intermediates of FLC were identified by UPLC‒MS/MS, and their transformation pathways were deduced by the condensed Fukui function (CFF) theory. Using sulfite/ClO2 as a pretreatment process to treat real potable water, aldehydes, ketones, carboxylic acids and other intermediates may be produced via the carboxylation and carbonylation reactions mediated by 1O2, therefore promoting the formation of DBPs during the following chlorination. This study provided a new perspective that while 1O2 is effectively produced in the sulfite/ClO2 process for contaminant degradation, the formation of DBPs during subsequent chlorination should be cautioned.

Covalent Adaptable Networks with Rapid UV Response Based on Reversible Thiol–Ene Reactions in Silicone Elastomers

Covalent Adaptable Networks with Rapid UV Response Based on Reversible Thiol–Ene Reactions in Silicone Elastomers

A Versatile Platform to Generate Shell-Cross-Linked Uniform Π-Conjugated Nanofibers with Controllable Length, High Morphological Stability, and Facile Surface Tailorability.

Living crystallization-driven self-assembly (CDSA) has emerged as an efficient route to generate π-conjugated-polymer-based nanofibers (CPNFs) with promising applications from photocatalysis to biomedicine. However, the lack of efficient tools to endow CPNFs with morphological stability and surface tailorability becomes a frustrating hindrance for expanding application spectrum of CPNFs. Herein, a facile strategy to fabricate length-controllable OPV-based (OPV = oligo(p-phenylenevinylene)) CPNFs containing a cross-linked shell with high morphological stability and facile surface tailorability through the combination of living CDSA and thiol-ene chemistry by using OPV5 -b-PNAAM32 (PNAAM = poly(N-allyl acrylamide)) as a model is reported. Uniform fiber-like micelles with tunable length can be generated by self-seeding of living CDSA. By taking advantage of radical thiol-ene reaction between vinyls of PNAAM corona and four-arm thiols, the shell of micelles can be cross-linked with negligible destruction of structure of vinylene-containing OPV core. The resulting micelles show high morphological stability in NaCl solution and PBS buffer, even upon heating at 80°C. The introduced extra thiol groups in the cross-linked shell can be further employed to install extra functional moieties via convenient thiol-Michael-type reaction. Given the negligible cytotoxicity of resulting CPNFs, this strategy opens an avenue to fabricate various CPNFs of diverse functionalities for biomedicine.

The Development and Mechanistic Study of an Iron-Catalyzed Intramolecular Nitroso Ene Reaction of Nitroarenes.

An intramolecular iron-catalyzed nitroso ene reaction was developed to afford six- or seven-membered N-heterocycles from nitroarenes using an earth abundant iron catalyst and phenylsilane as the terminal reductant. The reaction can be triggered using as little as 3 mol % of iron(II) acetate and 3 mol % of 4,7-dimethoxyphenanthroline as the ligand. The scope of the reaction is broad tolerating a range of electron-releasing or electron-withdrawing substituents on the nitroarene, and the ortho-substituent can be modified to diastereoselectively construct benzoxazines, dihydrobenzothiazines, tetrahydroquinolines, tetrahydroquinoxalines, or tetrahydrobenzooxazepines. Mechanistic investigations indicated that the reaction proceeds via a nitrosoarene intermediate, and kinetic analysis of the reaction revealed a first-order rate dependence in catalyst-, nitroarene-, and silane concentration, and an inverse kinetic order in acetate was observed. The difference in rates between PhSiH3 and PhSiD3 was found to be 1.50 ± 0.09, and investigation of the temperature dependence of the reaction rate revealed that the activation parameters to be ΔH‡ = 13.5 kcal•mol-1 and ΔS‡ = -39.1 cal•mol-1•K-1. These data were interpreted to indicate that the turnover-limiting step to be hydride transfer from iron to the coordinated nitroarene, which occurs through an ordered transition state with little Fe-H bond breaking.

Synthesis of mordenite by solvent-free method and its application in the dimethyl ether carbonylation reaction

Mordenite with different Si/Al ratios were synthesized by solvent-free method and used for dimethyl ether (DME) carbonylation reaction. The influence of Si/Al ratio in the feedstock on the structure, porosity and acid sites were systematically investigated. The characterization results showed that with the increase of Si/Al ratio in the feedstock, part of silicon species fail to enter the skeleton and the specific surface area and pore volume of the samples decreased. The amount of weak acid and medium strong acid decreased alongside with the increasing Si/Al ratio, and the amount of strong acid slightly increased. The Al atoms preferentially enter the strong acid sites in the 8 MR channel during the crystallization process. The high Si/Al ratio sample had more acid sites located in the 8 MR channel, leading to more active sites for carbonylation reaction and higher catalytic performance. Appropriately increasing the Si/Al ratio was beneficial for the improvement of carbonylation reaction activity over the MOR catalyst.

Activation of dimethyl carbonate on CeO2 surface: A combined experimental and theoretical study

Dimethyl carbonate (DMC) has recently emerged as a green reagent that finds versatile applications in methoxycarbonylation, carbonylation, and methylation reactions due to its multiple functionalities. In order to optimize the activity/selectivity of DMC-mediated heterogeneous catalytic reaction, it is imperative to enhance the fundamental understanding of the activation of DMC on the catalyst surface. In this study, the chemistry of DMC on the CeO2(111) surface was investigated using in-situ infrared spectroscopy, temperature-programmed surface reaction, and density functional theory calculations. It is shown that DMC readily converts into adsorbed methoxycarbonyl and methoxy on CeO2(111) at near room temperature. Upon heating, methoxycarbonyl decomposes into methoxy and carbonyl; the formed carbonyl could react with the surface oxygen atom (OS) of CeO2(111) to form desorbed carbon dioxide (COOS), leaving a surface oxygen vacancy. The surface methoxy groups undergo intermolecular hydrogen transfer to form CH3OH and HCHO, which upon heating either desorb or dehydrogenate with OS to form adsorbed methoxy and formate (with OSH), respectively. Adsorbed formate could react with OS to form desorbed COOS at higher temperatures. These findings provide fundamental insights into the catalytic chemistry of DMC on CeO2(111) surface, which may prove informative for the CeO2-catalyzed DMC-mediated reactions.

Dimethyl Ether Carbonylation on H-MOR Zeolite, Modified Cu, Co, Mg

Mordenite and ferrierite (Zeolyst International, H-form, SiO2/Al2O3 ≈ 20) were used to study the adsorption, thermally programmed desorption, and carbonylation of dimethyl ether (DME). The behavior of mordenite with Cu, Co, and Mg cations introduced by ion exchange has also been studied. DME carbonylation was carried out at 200°C, pressure 3 MPa, space velocity 8000 ml g–1 h–1 in a mixture, vol. %: ⁓2.2 DME, 92.8–95.5 CO, rest. N2. After the induction period, the methyl acetate content is about 4–5 times higher for mordenite compared to ferrierite. The formation of water, methanol and hydrocarbons was observed in small quantities. The introduction of Cu, Co, Mg cations into mordenite by ion exchange (single ion exchange, cation/Al ratio no more than 35%) not only increased the stability, but also increased the activity in the DME carbonylation reaction. It was found that an increase in the content of copper (from 1.19 to 2.23 wt %) and Mg (from 0.62 to 1.8 wt %) differently affects the activity. In the case of copper, an increase in activity was observed, while in the case of magnesium, the activity decreased. Preliminary reduction of copper-exchange mordenite leads to a decrease in activity and the appearance of metallic copper particles on the surface of mordenite crystallites. According to in situ diffuse reflectance infrared spectroscopy, the introduction of magnesium cations by triple ion exchange leads to a noticeable decrease in the number of Brønsted acid sites (BACs) in both the 12-MR and 8-MR channels of mordenite. The catalytic characteristics of ferrierite practically do not change when copper and magnesium are introduced by ion exchange.

Nickel-catalyzed acylzincation of allenes with organozincs and CO

Transition metal-catalyzed carbonylative reaction with CO gas are among the central task in organic synthesis, enabling the construction of highly valuable carbonyl compound. Here, we show an earth-abundant nickel-catalyzed three-component tandem acylzincation/cyclization sequence of allene and alkylzinc reagent with 1 atm of CO under mild conditions. This protocol is featured by broad functional group tolerance with high reaction selectivity, providing a rapid and convenient synthetic method for the construction of diverse fully substituted benzotropone derivatives. Mechanistic studies reveal that the installation of a cyano group tethered to allene moiety enables the high regio- and stereoselectivity of this acylzincation of allene, allowing the selective formation of three consecutive C-C bonds in a highly efficient manner.

Recent Advances in Nickel Catalyzed Carbonylative Reactionsviathe Insertion of Carbon Monoxide†

Comprehensive SummaryCarbonyl compounds have attracted considerable attention due to their extensive applications in drug discovery. Furthermore, they are important synthetic intermediates for the construction of carbon‐carbon and carbon‐heteroatom bonds. Transition‐metal‐catalyzed carbonylation via the insertion of CO is one of the most efficient and straightforward strategies to access carbonyl compounds. However, most of the transition‐metal‐catalyzed carbonylative reactions require expensive and toxic noble‐metal catalysts. Therefore, there is a growing demand for the exploration of nickel‐catalyzed carbonylative reactions via the insertion of CO due to the earth abundance and low cost of nickel. Compared with the well‐established palladium‐catalyzed carbonylative reactions, nickel‐catalyzed analogous transformations have been relatively underdeveloped. This is primarily because CO strongly binds to nickel, often resulting in catalyst poisoning. In recent years, some research groups have focused on using CO surrogates or NN2pincer nickel catalyst to circumvent the formation of Ni(CO)4. Nickel‐catalyzed carbonylation has been applied in the construction of carbonyl‐containing compounds, such as ketones, carboxylic acids, thioesters, acyl chloride and carboxamides.

Cyclic Oxygenate-Based Deactivation Mechanism in Dimethyl Ether Carbonylation Reaction over a Pyridine-Modified H-MOR Catalyst

Cyclic Oxygenate-Based Deactivation Mechanism in Dimethyl Ether Carbonylation Reaction over a Pyridine-Modified H-MOR Catalyst

Domino Three-Component N-Acylation/[4 + 2] Cycloaddition/Alder-ene Synthesis of Polysubstituted Benzo[f]isoindole-4-carboxylic Acids.

Diversely substituted, partially saturated benzo[f]isoindole-4-carboxylic acids were synthesized by a new three-component reaction (3CR) starting from cinnamic amines (3-arylallylamines), maleimides, and maleic anhydride. The process consists of N-acylation of the amines by maleic anhydride, intramolecular [4 + 2] cycloaddition in vinylarenes (the IMDAV reaction), and the concluding Alder-ene reaction between Diels-Alder intermediates and maleimides. All of the reaction steps proceed in a highly regio- and stereoselective manner, furnishing five adjacent chiral centers and leading to a single diastereoisomer of the title compound. The efficiency of the transformation is secured by thermal conditions or utilization of soft Lewis acids (Yb(OTf)3) as catalysts. The kinetics and mechanism of the 3CR were studied by using dynamic 19F NMR. Based on the NMR data and density functional theory (DFT) calculations, the IMDAV, not the Alder-ene, reaction is the rate-limiting step of the entire process.

Radical‐Mediated Scission of Thioaminals for On‐Demand Construction‐Then‐Destruction of Cross‐Linked Polymer Networks

AbstractTwo‐stage polymerizing‐then‐degrading networks are achieved by exposure to a single near UV light source, by sequentially performing thiol–ene photopolymerization and radical‐mediated thioaminal scission. To understand the mechanisms involved, synthesis of model thioaminal small molecules shows photo‐activated thioaminal scission produces thioamide moieties, identifiable by distinct NMR singlets at 3.29 and 3.26 ppm and a Fourier Transform IR (FTIR) peak ≈1530 cm−1. The scission process is proposed to occur via ß‐scission of the carbon next to the sulfur atom and is found to be influenced by thiol substitution on the thioaminal, leading to scission conversion increasing from 5 ± 1 to 39 ± 3% and scission time decreasing from 6 to 2 min as the thiols become progressively more substituted. Thioaminal scission occurs semi‐orthogonally with radical‐mediated thiol–ene reactions; the thiol–ene reaction achieves near quantitative yield within the first 0.5 min while thioaminal scission requires a further 5–15 min. This semi‐orthogonality is exploited to create two‐stage polymerizing‐then‐degrading networks, with both regimes dependent on total light dose from a single light source and the transition occurring ≈2 J cm−2 under these exposure and polymerization conditions. This work establishes thioaminals as a new photo‐mediated scission chemistry and a means to create multi‐stage, light‐activated networks.

Vapor-phase ethanol carbonylation over Ni supported on activated carbon: Influence of the textural properties and oxygen-containing groups

The performance of ethanol carbonylation for Ni supported on different activated carbons varies considerably. The physicochemical properties of Ni catalysts supported on different activated carbons have been investigated in detail by a series of characterization studies. Catalysts with less oxygen-containing groups and smaller pore size are demonstrated to be more effective for vapor-phase ethanol carbonylation, with higher ethanol conversion and selectivity of propionate and ethyl propionate. However, there is no clear correlation between the carbonylation activity and the initial Ni nanoparticles size of the fresh catalysts due to the re-dispersion of the Ni nanoparticles by the ethane iodide interaction during the reaction. It is also proved that the deactivation of the catalyst may be caused by the loss of the active component Ni and the deposition of oxygen-containing carbon species. ​In situ diffuse reflectance infrared Fourier transform spectroscopy (in-situ DRIFTS) showed that ethane iodide is essential for the ethanol carbonylation reaction and that carbonylation intermediates (C2H5CO-Ni-I) are formed only in the presence of ethane iodide. The mechanism of the ethanol carbonylation reaction was proposed, showing that the carbonylation of CO insertion and the elimination of ethylene production in the intermediate are competing reactions. This work has implications for the design of highly efficient alcohol carbonylation catalysts.

Evidence through Thermal Analysis of Retro Diels-Alder Reaction in Model Networks Based on Anthracene Modified Polyester Resins.

The present work is focused on polyester resins obtained from the diglycidyl ether of bisphenol A and anthracene modified 5-maleimidoisophthalic acid. Because the maleimide-anthracene Diels-Alder (DA) adduct is stable at high temperatures, it is considered a good option for high performance polymers. However, the information related to the retroDA reaction for this type of adduct is sometimes incoherent. A detailed thermal study (conventional TGA, HiRes TGA, MTGA, DSC, MDSC) was performed in order to establish whether the rDA reaction can be revealed for this type of anthracene modified polyester resins. The TGA method confirmed the cleavage of the anthracene-maleimide DA adduct, while the DSC demonstrated the presence of anthracene in the system. At high temperatures, unprotected maleimide homopolymerizes and/or reacts with allyl groups according to the -ene reaction. Therefore, the thermal DA reaction is not displayed anymore upon the subsequent cooling, and the glass transition region is registered at a higher temperature range during the second heating. The use of sample-controlled thermal analysis (HiRes TGA) and MTGA improved the TGA result; however, it was not possible to separate the very complex degradation processes that are interconnected.